Modern day gladiators, the best mixed martial artists (MMAers) like Khabib Nurmagomedov, Jon Jones, Anderson Silva, Georges St-Pierre, and Fedor Emelianenko, shown above, are multidimensional, successfully combining stand up and ground-based combat to submit (“tap out”), render unconscious (“knockout/KO”), prompt a referee stoppage (“technical knockout/TKO”), or outpoint their opponents.
The lead EpicentRx therapy, AdAPT-001, is also a ‘hybrid fighter’ that combines different lines of attack to hopefully finish off its opponent, cancer.
The first one is the “clinch.” In the clinch, AdAPT-001 binds tenaciously to cancer cells via the coxsackievirus and adenovirus receptor (CAR).
The second is the “takedown” in which AdAPT-001 establishes “mount” control over the transcription and translation machinery that are necessary for viral production and expression of the TGF-β trap transgene, which AdAPT-001 carries.
The third is “ground-and-pound” in which AdAPT-001 heavily damages tumors through so much self-replication and TGF-β trap expression that it culminates in lysis or rupture of the cancer cells, and release of tumor antigens, danger signals, proinflammatory cytokines, and new viral particles.
The fourth is “submission.” In this final phase, the lysis of cancer cells combined with expression of the TGF-β trap, which binds to and eliminates the immunosuppressive cytokine, TGF-β, activates the immune system to target tumors wherever they are and to make them, hopefully, “tap out.” The odds of a successful submission increase tremendously when a checkpoint inhibitor (CI) is added to the mix, as results from a Phase 2 trial with AdAPT-001 plus a CI demonstrate primarily in a tumor type that develops in soft tissues like muscle, tendons, fat, lymph and blood vessels, and nerves called sarcomas.
To date, the success of AdAPT-001 is a testament to the hard work of its “trainers” and “cornermen”, Drs. Tony Reid, and Christopher Larson from EpicentRx and Anthony P. Conley from MD Anderson, who equipped it with a “hybrid fighting style”, that is direct tumor lysis, and TGF-β trap expression as well as with what appears to be a winning game plan in sarcomas plus a checkpoint inhibitor.
However, AdAPT-001 is still in early Phase 2 clinical trials and must conclusively and unequivocally demonstrate evidence of efficacy in larger, more well-powered trials before it can receive FDA approval. So, in other words, to paraphrase an old expression, this contest between AdAPT-001 and cancer “ain’t over until the FDA signs (off).”